Prostaglandin E2 derived from phosphatidylinositol breakdown in the exocrine pancreas facilitates secretion by an action on the ducts.
The observation that stimulation of a variety of endocrine and exocrine glands, synaptic tissue and certain other structures with appropriate agonists is associated with a breakdown of phosphatidylinositol (PI) and a synthesis of phosphatidic acid (accompanied by increased turnover) has long been known. Our laboratory recently showed that arachidonate released from PI breakdown forms prostaglandin (PG) E2 and the latter is involved in secretagogue-stimulated secretion from the exocrine pancreas. The data presented here are consistent with the view that there is a "pool" of enzymes in the ducts that is released by PGE2, whether added exogenously or generated by carbamylcholine-stimulated PI breakdown and that this release is probably brought about by relaxation of the ampulla of Vater and possibly effects on smooth muscle of the ducts. This hypothesis is supported by the following observations. Involvement of PGs (inhibition of carbamylcholine-stimulated secretion by indomethacin or phenylbutazone) can be demonstrated only in the intact mouse pancreas and not in sliced pancreas or acinar cells, even though PI breakdown can be demonstrated in the cells. The smooth muscle relaxants, nitroglycerin and sodium nitrite, increase amylase release. Secretin, which stimulates fluid secretion from the ducts (acini in mouse and rat) but not enzyme secretion from the acini, increases secretion to the same extent as PGE2. Secretin is believed to increase enzyme secretion by a "washout" effect in the ducts. PGE2 gave no further increase in enzyme secretion in the presence of secretin. The effects of none of these agents (smooth muscle relaxants, secretin or PGE2) are additive.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002108:Ceruletide / Q000494:pharmacology; D015232:Dinoprostone; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis / Q000502:physiology*; D012633:Secretin / Q000494:pharmacology
D001095:Arachidonic Acids; D009125:Muscle Relaxants, Central; D010716:Phosphatidylinositols; D011458:Prostaglandins E; D012633:Secretin; D016718:Arachidonic Acid; D002108:Ceruletide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone